This Career Development Plan will ensure Dr. Marie-Claude Hofmann's success as an independent research scientist in the Department of Biology, University of Dayton. Dr. Hofmann's general area of interest is the biology of spermatogonial stem cells (SSCs), the Asingle spermatogonia. There is great interest in the Asingle spermatogonia because of their importance for understanding basic mechanisms of cell self-renewal versus differentiation, for the treatment of reproductive dysfunction, and for the understanding of the etiology of testicular cancer, in particular seminoma. However, studies on the biology of these cells have been severely hampered because their number is low, no unique marker exists and it has been difficult to physically separate them from the other more mature spermatogonia. Dr. Hofmann's team recently developed a method that allows the isolation of pure populations of SSCs, and has started to study their behavior in vitro. Using microarrays, they also have analyzed the transcriptional program of SSCs in the presence of glial cell line derived neurotrophic factor (GDNF), a growth factor produced by Sertoli cells. One of Dr. Hofmann's research objectives is to elucidate the signaling pathways induced by GDNF that promote SSCs renewal and differentiation. In the first aim, Asingle spermatogonia will be isolated and their clonogenic potential evaluated by germ cell transplantations. In the second aim, they will determine which signaling pathways are induced by GDNF, leading to Asingle spermatogonia self-renewal or differentiation. In the third aim, they will study how GDNF interacts with other growth factors/receptors to promote self-renewal or differentiation. This work will expand the knowledge of the functional characteristics of the Asingle spermatogonia and lend better insight into the molecular mechanisms that drive the first steps of spermatogenesis. In particular, the role of the growth factor GDNF in regulating self-renewal and/or differentiation will be elucidated. This Career Development Plan will assist Dr. Hofmann in accomplishing her goals. Specifically, it will release her from substantial teaching, thereby allowing her to devote full attention to research, increasing her skills in specific areas of biomedical science and technology. In addition, Dr. Hofmann will not be required to serve on administrative committees, and be released from undergraduate advising duties. At the University of Dayton, the Department of Biology, the College of Arts &Sciences and the Graduate School will provide a supportive environment for the development of Dr. Hofmann's research career. The University of Dayton has recently committed considerable resources to promote interdisciplinary bioscience and engineering research, and Dr. Hofmann is a vital member of our core group of lead investigators. This award will allow her to further collaborations with other departments at our University as well as collaborations with other institutions.